Nerve growth factor links oral cancer progression, pain, and cachexia

Mol Cancer Ther. 2011 Sep;10(9):1667-76. doi: 10.1158/1535-7163.MCT-11-0123. Epub 2011 Jul 12.

Abstract

Cancers often cause excruciating pain and rapid weight loss, severely reducing quality of life in cancer patients. Cancer-induced pain and cachexia are often studied and treated independently, although both symptoms are strongly linked with chronic inflammation and sustained production of proinflammatory cytokines. Because nerve growth factor (NGF) plays a cardinal role in inflammation and pain, and because it interacts with multiple proinflammatory cytokines, we hypothesized that NGF acts as a key endogenous molecule involved in the orchestration of cancer-related inflammation. NGF might be a molecule common to the mechanisms responsible for clinically distinctive cancer symptoms such as pain and cachexia as well as cancer progression. Here we reported that NGF was highly elevated in human oral squamous cell carcinoma tumors and cell cultures. Using two validated mouse cancer models, we further showed that NGF blockade decreased tumor proliferation, nociception, and weight loss by orchestrating proinflammatory cytokines and leptin production. NGF blockade also decreased expression levels of nociceptive receptors TRPV1, TRPA1, and PAR-2. Together, these results identified NGF as a common link among proliferation, pain, and cachexia in oral cancer. Anti-NGF could be an important mechanism-based therapy for oral cancer and its related symptoms.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Cachexia / etiology*
  • Carcinoma, Squamous Cell / complications*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mouth Neoplasms / complications*
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Nerve Growth Factor / antagonists & inhibitors
  • Nerve Growth Factor / metabolism*
  • Pain / drug therapy
  • Pain / etiology*
  • Pain Measurement / drug effects
  • RNA, Messenger / metabolism
  • Receptor, PAR-2 / metabolism
  • Staining and Labeling
  • TRPV Cation Channels / metabolism
  • Transient Receptor Potential Channels / metabolism
  • Weight Loss / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Cytokines
  • RNA, Messenger
  • Receptor, PAR-2
  • TRPV Cation Channels
  • Transient Receptor Potential Channels
  • Nerve Growth Factor